title: Vgamma1+ T cells and tumor necrosis factor-alpha in ozone-induced airway hyperresponsiveness.
abstract: gammadelta T cells regulate airway reactivity, but their role in ozone (O3)-induced airway hyperresponsiveness (AHR) is not known. Our objective was to determine the role of gammadelta T cells in O3-induced AHR. Different strains of mice, including those that were genetically manipulated or antibody-depleted to render them deficient in total gammadelta T cells or specific subsets of gammadelta T cells, were exposed to 2.0 ppm of O3 for 3 hours. Airway reactivity to inhaled methacholine, airway inflammation, and epithelial cell damage were monitored. Exposure of C57BL/6 mice to O3 resulted in a transient increase in airway reactivity, neutrophilia, and increased numbers of epithelial cells in the lavage fluid. TCR-delta(-/-) mice did not develop AHR, although they exhibited an increase in neutrophils and epithelial cells in the lavage fluid. Similarly, depletion of gammadelta T cells in wild-type mice suppressed O3-induced AHR without influencing airway inflammation or epithelial damage. Depletion of Vgamma1+, but not of Vgamma4+ T cells, reduced O3-induced AHR, and transfer of total gammadelta T cells or Vgamma1+ T cells to TCR-delta(-/-) mice restored AHR. After transfer of Vgamma1+ cells to TCR-delta(-/-) mice, restoration of AHR after O3 exposure was blocked by anti-TNF-alpha. However, AHR could be restored in TCR-delta(-/-)mice by transfer of gammadelta T cells from TNF-alpha-deficient mice, indicating that another cell type was the source of TNF-alpha. These results demonstrate that TNF-alpha and activation of Vgamma1+ gammadelta T cells are required for the development of AHR after O3 exposure.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health and the University of Colorado Health Sciences Center, Denver, Colorado, USA.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsubara
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Niyun
authors.initials: N
authors.lastname: Jin
authors.forename: Masakazu
authors.initials: M
authors.lastname: Okamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsuda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Park
authors.forename: Glen
authors.initials: G
authors.lastname: McConville
authors.forename: Anthony
authors.initials: A
authors.lastname: Joetham
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002452:Cell Count; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010126:Ozone; D011014:Pneumonia / Q000150:complications / Q000276:immunology / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000378:metabolism*
chemical_list: D000906:Antibodies; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone